The major objectives of this research are to obtain an understanding of: (1) the regulation of fatty acid biosynthesis and the control of the developmental changes thereof in mammalian liver and brain, and (2) the mechanisms underlying the regulation and development of the fatty acid synthetase (FAS), a multienzyme complex, in these mammalian tissues. Pursuit of these objectives is very much intertwined. We will utilize immunochemical techniques to study enzyme content; similar techniques, after appropriate labeling with radioactive precursors, will be utilized in developing animals to study synthesis and degradation of complex and turnover of the characteristic prosthetic group of the synthetase. The latter turnover appears to represent a unique regulatory mechanism and may be involved particularly in fine and rapid control of synthetase activity. The important effectors of the synthetase-nutritional and hormonal factors, cyclic mononucleotides, certain drugs, genetic mutation (e.g., obese mice)--will be delineated and their effect on enzyme and prosthetic group turnover determined for developing brain and liver. The synthetase of brain will be purified and characterized, with studies particularly designed to define bases for differences in regulation of FAS of brain and liver and in catalytic function of both of these complexes with development. Regulation of fatty acid biosynthesis in neural and glial cells in culture will be carried out to study this critical process at the cellular level. Although a number of lipogenic enzymes will be monitored, the detailed studies of mechanisms of changes in activity and content will probably be confined to the synthetase and will include determination of enzyme snthesis and degradation and prosthetic group turnover. In addition to study of certain effectors the role of fatty acid biosynthesis and the synthetase, specifically, in neuronal (and glial) differentiation will be elucidated. The relationship of the synthetase to this particular process of membrane biogenesis will be of considerable additional interest, since there is experimental evidence in microorganisms and circumstantial evidence in mammalian tissues that synthetase is specifically linked to membrane phospholipid synthesis. The relation of FAS to various factors that affect membrane biogenesis (certain of the hormones, drugs to be evaluated in both the in vivo and culture studies) wil (Text Truncated - Exceeds Capacity)